Murine monoclonal antibodies are not useful for repeated administration to man because of the number of foreign antigen determinants they contain. Production of human monoclonal antibodies would be desirable for a variety of approaches in prophylaxis and therapy of disease, and also in protection against contact with noxious agents. We propose development of a procedure that will permit rapid isolation of composite human monoclonal antibodies in which pre-selected mouse variable regions have been substituted for the human variable regions conveying any desired specificity to the human antibody. The procedures proposed involve a minimum of in vitro DNA reconstruction work or clone screening and therefore would be applicable for production of a wide variety of antibodies. Potential applications include pre-treatment of individuals exposed to infectious or toxic agents and rapid protection against spread of infections.